Ethoxzolamide
Explore a selection of our essential drug information below, or:
Overview
- DrugBank ID
- DB00311
- Type
- Small Molecule
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 0
- Phase 2
- 0
- Phase 3
- 0
- Phase 4
- 0
- Mechanism of Action
- Carbonic anhydrase 2Inhibitor
- Carbonic anhydrase 4Inhibitor
- Carbonic anhydrase 7Inhibitor
- + 1 more target
- Carbonic anhydrase 2
Identification
- Generic Name
- Ethoxzolamide
- DrugBank Accession Number
- DB00311
- Background
Ethoxzolamide is a sulfonamide used as diuretic and in glaucoma. It inhibits carbonic anhydrase activity in proximal renal tubules to decrease reabsorption of water, sodium, potassium, bicarbonate. Its pharmacological activity thus confers the risk for hypokalemia.
- Type
- Small Molecule
- Groups
- Withdrawn
- Structure
- Weight
- Average: 258.317
Monoisotopic: 258.013283576 - Chemical Formula
- C9H10N2O3S2
- Synonyms
- 6-Ethoxy-1,3-benzothiazole-2-sulfonamide
- Ethoxazolamide
- Ethoxyzolamide
Pharmacology
- Indication
For use in the treatment of duodenal ulcers, as a diuretic, and in the treatment of glaucoma, and may also be useful in the treatment of seizures associated with epilepsy.
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- Pharmacodynamics
Ethoxzolamide is an inhibitor of the carbonic anhydrase enzyme in proximal renal tubules that works by decreasing the reabsorption of water, sodium, potassium, bicarbonate. It also decreases the activity of carbonic anhydrase expressed in the CNS, which leads to increased seizure threshold. Inhibition of carbonic anhydrase in the eye contributes to its effect of reducing intraocular pressure and decreasing aqueous humor.
- Mechanism of action
Ethoxzolamide binds to and inhibits carbonic anhydrase I, which plays an essential role in facilitating the transport of CO2 and H+ in the intracellular space, across biological membranes, and in the layers of the extracellular space. Through inhibition of the enzyme, the balance of applicable membrane equilibrium systems are affected.
Target Actions Organism ACarbonic anhydrase 2 inhibitorHumans ACarbonic anhydrase 4 inhibitorHumans ACarbonic anhydrase 7 inhibitorHumans ACarbonic anhydrase 1 inhibitorHumans UCarbonic anhydrase 3 inhibitorHumans - Absorption
Rapidly absorbed with 65% bioavailability
- Volume of distribution
Not Available
- Protein binding
~89%
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
2.5-5.5 hours
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Ethoxzolamide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy. Acamprosate The excretion of Acamprosate can be decreased when combined with Ethoxzolamide. Acarbose The therapeutic efficacy of Acarbose can be increased when used in combination with Ethoxzolamide. Aceclofenac Ethoxzolamide may increase the excretion rate of Aceclofenac which could result in a lower serum level and potentially a reduction in efficacy. Acemetacin The therapeutic efficacy of Ethoxzolamide can be decreased when used in combination with Acemetacin. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Cardrase (PHARMACIA AND UPJOHN) / Ethamide (ALLERGAN)
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzothiazoles. These are organic compounds containing a benzene fused to a thiazole ring (a five-membered ring with four carbon atoms, one nitrogen atom and one sulfur atom).
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzothiazoles
- Sub Class
- Not Available
- Direct Parent
- Benzothiazoles
- Alternative Parents
- Alkyl aryl ethers / Organosulfonamides / Benzenoids / Thiazoles / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides show 1 more
- Substituents
- 1,3-benzothiazole / Alkyl aryl ether / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Ether / Heteroaromatic compound / Hydrocarbon derivative show 12 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- benzothiazoles, sulfonamide (CHEBI:101096)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Z52H4811WX
- CAS number
- 452-35-7
- InChI Key
- OUZWUKMCLIBBOG-UHFFFAOYSA-N
- InChI
- InChI=1S/C9H10N2O3S2/c1-2-14-6-3-4-7-8(5-6)15-9(11-7)16(10,12)13/h3-5H,2H2,1H3,(H2,10,12,13)
- IUPAC Name
- 6-ethoxy-1,3-benzothiazole-2-sulfonamide
- SMILES
- CCOC1=CC2=C(C=C1)N=C(S2)S(N)(=O)=O
References
- Synthesis Reference
Korman, J.; U.S. Patent 2,868,800; January 13, 1959; assigned to The Upjohn Company.
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014456
- KEGG Drug
- D02441
- PubChem Compound
- 3295
- PubChem Substance
- 46509023
- ChemSpider
- 3179
- BindingDB
- 10882
- ChEBI
- 101096
- ChEMBL
- CHEMBL18
- ZINC
- ZINC000000056721
- Therapeutic Targets Database
- DAP000598
- PharmGKB
- PA164754743
- PDBe Ligand
- EZL
- Wikipedia
- Ethoxzolamide
- PDB Entries
- 3caj / 3dcw / 3dd0 / 3mdz / 5jn9 / 5tt3 / 6bcc / 6mwi / 6ql2
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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Pharmacoeconomics
- Manufacturers
- Pharmacia and upjohn co
- Allergan pharmaceutical
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 188-190.5 Korman, J.; U.S. Patent 2,868,800; January 13, 1959; assigned to The Upjohn Company. water solubility 40 mg/L YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 2.01 HANSCH,C ET AL. (1995) logS -3.81 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 0.688 mg/mL ALOGPS logP 1.87 ALOGPS logP 1.6 Chemaxon logS -2.6 ALOGPS pKa (Strongest Acidic) 7.51 Chemaxon pKa (Strongest Basic) -1.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 82.28 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 59.97 m3·mol-1 Chemaxon Polarizability 25.27 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.8667 Caco-2 permeable - 0.6038 P-glycoprotein substrate Non-substrate 0.6875 P-glycoprotein inhibitor I Non-inhibitor 0.8793 P-glycoprotein inhibitor II Non-inhibitor 0.9528 Renal organic cation transporter Non-inhibitor 0.8576 CYP450 2C9 substrate Non-substrate 0.8346 CYP450 2D6 substrate Non-substrate 0.7982 CYP450 3A4 substrate Non-substrate 0.6017 CYP450 1A2 substrate Inhibitor 0.6223 CYP450 2C9 inhibitor Inhibitor 0.62 CYP450 2D6 inhibitor Non-inhibitor 0.8842 CYP450 2C19 inhibitor Inhibitor 0.6582 CYP450 3A4 inhibitor Non-inhibitor 0.6471 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5599 Ames test Non AMES toxic 0.5832 Carcinogenicity Non-carcinogens 0.7065 Biodegradation Not ready biodegradable 0.9846 Rat acute toxicity 2.5056 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9429 hERG inhibition (predictor II) Non-inhibitor 0.8419
Spectra
- Mass Spec (NIST)
- Download (10.1 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 162.4085459 predictedDarkChem Lite v0.1.0 [M-H]- 162.8913459 predictedDarkChem Lite v0.1.0 [M-H]- 151.90479 predictedDeepCCS 1.0 (2019) [M+H]+ 162.8070459 predictedDarkChem Lite v0.1.0 [M+H]+ 163.2533459 predictedDarkChem Lite v0.1.0 [M+H]+ 154.2628 predictedDeepCCS 1.0 (2019) [M+Na]+ 162.9455459 predictedDarkChem Lite v0.1.0 [M+Na]+ 163.0169459 predictedDarkChem Lite v0.1.0 [M+Na]+ 160.35606 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the reversible hydration of carbon dioxide (PubMed:11327835, PubMed:11802772, PubMed:11831900, PubMed:12056894, PubMed:12171926, PubMed:1336460, PubMed:14736236, PubMed:15300855, PubMed:15453828, PubMed:15667203, PubMed:15865431, PubMed:16106378, PubMed:16214338, PubMed:16290146, PubMed:16686544, PubMed:16759856, PubMed:16807956, PubMed:17127057, PubMed:17251017, PubMed:17314045, PubMed:17330962, PubMed:17346964, PubMed:17540563, PubMed:17588751, PubMed:17705204, PubMed:18024029, PubMed:18162396, PubMed:18266323, PubMed:18374572, PubMed:18481843, PubMed:18618712, PubMed:18640037, PubMed:18942852, PubMed:1909891, PubMed:1910042, PubMed:19170619, PubMed:19186056, PubMed:19206230, PubMed:19520834, PubMed:19778001, PubMed:7761440, PubMed:7901850, PubMed:8218160, PubMed:8262987, PubMed:8399159, PubMed:8451242, PubMed:8485129, PubMed:8639494, PubMed:9265618, PubMed:9398308). Can also hydrate cyanamide to urea (PubMed:10550681, PubMed:11015219). Stimulates the chloride-bicarbonate exchange activity of SLC26A6 (PubMed:15990874). Essential for bone resorption and osteoclast differentiation (PubMed:15300855). Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption
- Specific Function
- arylesterase activity
- Gene Name
- CA2
- Uniprot ID
- P00918
- Uniprot Name
- Carbonic anhydrase 2
- Molecular Weight
- 29245.895 Da
References
- Mincione F, Scozzafava A, Supuran CT: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14(7):649-54. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH (PubMed:15563508, PubMed:16686544, PubMed:16807956, PubMed:17127057, PubMed:17314045, PubMed:17652713, PubMed:17705204, PubMed:18618712, PubMed:19186056, PubMed:19206230, PubMed:7625839). May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis (PubMed:15563508). It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid (PubMed:15563508)
- Specific Function
- carbonate dehydratase activity
- Gene Name
- CA4
- Uniprot ID
- P22748
- Uniprot Name
- Carbonic anhydrase 4
- Molecular Weight
- 35032.075 Da
References
- Mincione F, Scozzafava A, Supuran CT: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14(7):649-54. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Reversible hydration of carbon dioxide
- Specific Function
- carbonate dehydratase activity
- Gene Name
- CA7
- Uniprot ID
- P43166
- Uniprot Name
- Carbonic anhydrase 7
- Molecular Weight
- 29658.235 Da
References
- Mincione F, Scozzafava A, Supuran CT: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14(7):649-54. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the reversible hydration of carbon dioxide (PubMed:10550681, PubMed:16506782, PubMed:16686544, PubMed:16807956, PubMed:17127057, PubMed:17314045, PubMed:17407288, PubMed:18618712, PubMed:19186056, PubMed:19206230). Can hydrate cyanamide to urea (PubMed:10550681)
- Specific Function
- arylesterase activity
- Gene Name
- CA1
- Uniprot ID
- P00915
- Uniprot Name
- Carbonic anhydrase 1
- Molecular Weight
- 28870.0 Da
References
- Kohling R, Vreugdenhil M, Bracci E, Jefferys JG: Ictal epileptiform activity is facilitated by hippocampal GABAA receptor-mediated oscillations. J Neurosci. 2000 Sep 15;20(18):6820-9. [Article]
- Perez Velazquez JL: Bicarbonate-dependent depolarizing potentials in pyramidal cells and interneurons during epileptiform activity. Eur J Neurosci. 2003 Sep;18(5):1337-42. [Article]
- Heck RW, Tanhauser SM, Manda R, Tu C, Laipis PJ, Silverman DN: Catalytic properties of mouse carbonic anhydrase V. J Biol Chem. 1994 Oct 7;269(40):24742-6. [Article]
- Siffert W, Gros G: Carbonic anhydrase C in white-skeletal-muscle tissue. Biochem J. 1982 Sep 1;205(3):559-66. [Article]
- Scozzafava A, Briganti F, Ilies MA, Supuran CT: Carbonic anhydrase inhibitors: synthesis of membrane-impermeant low molecular weight sulfonamides possessing in vivo selectivity for the membrane-bound versus cytosolic isozymes. J Med Chem. 2000 Jan 27;43(2):292-300. [Article]
- Bertucci A, Innocenti A, Zoccola D, Scozzafava A, Tambutte S, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8. doi: 10.1016/j.bmc.2009.05.063. Epub 2009 May 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Reversible hydration of carbon dioxide
- Specific Function
- carbonate dehydratase activity
- Gene Name
- CA3
- Uniprot ID
- P07451
- Uniprot Name
- Carbonic anhydrase 3
- Molecular Weight
- 29557.215 Da
References
- Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 09, 2024 05:52